rTMS for Cognitive Impairment in Parkinson's Disease

(TMSCogReP Trial)

Recruiting at 1 trial location

Overseen By Elyse R Walsh, DPT

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Tricyclics, Neuroleptics, others

Disqualifiers: Dementia, Severe depression, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a non-invasive treatment called repetitive transcranial magnetic stimulation (rTMS) to determine its potential to improve thinking skills in Veterans with Parkinson's disease or atypical parkinsonism. Researchers aim to assess the safety of this treatment and its effects on the brain and behavior. The trial includes two groups: one will receive active rTMS, and the other will receive a sham (fake) version for comparison. Veterans with mild memory or thinking issues who are on stable medication are suitable candidates for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You will need to stay on your current medications without any changes in type or dose during the trial.

What prior data suggests that rTMS is safe for cognitive impairment in Parkinson's disease?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for people with Parkinson's disease. Studies have found that patients usually tolerate rTMS well, with few reports of serious side effects. For instance, some trials noted only mild and temporary discomfort at the stimulation site. Some patients might experience headaches, but these typically don't last long.

Other studies have used rTMS to help improve movement problems in Parkinson's patients, and safety data from these treatments suggest it might also be safe for enhancing thinking skills. Since this trial is in the early stages, the main goal is to confirm this safety before moving to larger studies.

Overall, while rTMS seems promising, it remains under study. Participants should always discuss potential risks and benefits with their doctors before joining any clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about rTMS (repetitive transcranial magnetic stimulation) for cognitive impairment in Parkinson's disease because it offers a non-invasive approach that directly targets brain activity. Unlike traditional medications like levodopa and dopamine agonists, which primarily focus on motor symptoms, rTMS aims to improve cognitive functions by stimulating specific brain regions with magnetic pulses. This technique allows for precise modulation of brain activity, which could lead to cognitive improvements without the systemic side effects associated with drug therapies. The promise of rTMS lies in its potential to enhance quality of life for those with Parkinson's by addressing cognitive issues that current treatments don't adequately tackle.

What evidence suggests that rTMS is effective for cognitive impairment in Parkinson's disease?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can improve thinking skills in people with Parkinson's disease. In this trial, participants will receive either active rTMS or sham rTMS. Studies have found that active rTMS can boost mental function, reduce depression, and even aid walking in these patients. One study discovered that high-frequency rTMS on specific brain areas, such as the dorsolateral prefrontal cortex (DLPFC), was particularly effective in enhancing thinking abilities. Another review suggested that rTMS could be a promising tool for improving thinking skills in conditions like mild cognitive impairment. Overall, early findings are encouraging for its potential to address thinking problems in Parkinson’s disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Sandra L. Kletzel, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

This trial is for Veterans over 50 with Parkinson's disease who have mild cognitive impairment, can speak and read English, and are treated at Hines VA Hospital or Jesse Brown VA Medical Center. Participants must be on stable medication that won't change during the study. Those with severe depression, dementia, certain implants, history of seizures or metal in their body cannot join.

Inclusion Criteria

My current medication is stable and will not change during the trial.

I am 50 years old or older.

My medication and its dose have been stable and will remain so during the trial.

Exclusion Criteria

You have memory and thinking problems.

Your motor threshold cannot be measured accurately for determining the dosage of rTMS.

I am not taking medications known to increase the risk of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham rTMS treatment to assess cognitive outcomes and brain connectivity

8 weeks

Regular sessions for rTMS treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a neurocognitive battery assessment

4 weeks

1 visit (in-person) for follow-up assessment

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The trial tests if repetitive transcranial magnetic stimulation (rTMS) using a MagVenture MagProX100 stimulator can improve thinking abilities in those with Parkinson's experiencing mild cognitive issues. It assesses the safety and effects of rTMS on behavior and brain function.

How Is the Trial Designed?

Group I: active rTMS Experimental Treatment 1 Intervention

For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.

Group II: sham rTMS Placebo Group 1 Intervention

For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study involving 26 patients with mild to moderate Parkinson's disease, 50-Hz repetitive transcranial magnetic stimulation (rTMS) was found to be safe, with no adverse effects or increased risk of cortical excitability.

However, the treatment did not lead to significant improvements in motor symptoms such as gait and bradykinesia, although there was a brief improvement in daily living activities, suggesting that longer or different rTMS protocols may be needed for better efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease. Benninger, DH., Iseki, K., Kranick, S., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

Repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) both showed significant improvements in motor function for Parkinson's disease patients compared to sham stimulation, with rTMS having a moderate effect size (SMD = 0.394) and TES showing a larger effect (SMD = 0.611).

Neither rTMS nor TES were found to improve cognitive function in patients with Parkinson's disease, indicating that while these therapies can help with motor symptoms, they may not address cognitive deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis. Goodwill, AM., Lum, JAG., Hendy, AM., et al.[2022]

Deep repetitive transcranial magnetic stimulation (drTMS) is safe for patients with various Parkinson Syndromes and can effectively reduce their self-reported motor symptom severity and depression, based on a retrospective analysis of 21 patients.

The treatment showed more significant benefits in older patients with Parkinson's disease, although it did not demonstrate any improvement in cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil. Cont, C., Lehto, A., Stute, N., et al.[2022]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a study involving 6 patients with Parkinson's disease and 10 normal controls, repetitive transcranial magnetic stimulation (rTMS) significantly improved choice reaction time and movement time in patients without affecting their error rate, suggesting enhanced motor function.

The rTMS treatment also improved performance on a grooved peg-board test in Parkinson's patients, particularly when they were not on medication, indicating its potential as a therapeutic intervention for motor symptoms in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Pascual-Leone, A., Valls-Solé, J., Brasil-Neto, JP., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) at different frequencies (1 Hz and 5 Hz) significantly improved motor function and daily living activities in patients with Parkinson's disease, as evidenced by clinical rating scores and motor dexterity assessments in a study involving 50 participants.

The study demonstrated that rTMS induced changes in brain activity, with increased blood oxygen level-dependent (BOLD) signals in motor areas, indicating that rTMS can promote cortical plasticity and potentially restore motor function in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of 1 Hz Inhibitory and 5 Hz Excitatory Repetitive Transcranial Magnetic Stimulations in Parkinson's Disease: A Functional Magnetic Resonance Imaging Study. Bhat, P., Goyal, V., Kumaran, SS., et al.[2023]

In a study involving 12 patients with idiopathic Parkinson's disease, 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex significantly improved daily living activities and motor scores, while occipital rTMS showed no significant clinical effects.

The study suggests that rTMS may have indirect effects on subcortical structures that contribute to symptom improvement, despite reduced regional cerebral blood flow (rCBF) in the stimulated areas, indicating a complex mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. Ikeguchi, M., Touge, T., Nishiyama, Y., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has shown a significant positive effect on global cognitive function in Parkinson's disease patients, particularly measured by the mini-mental state examination (MMSE) across 14 studies with 173 subjects.

High-frequency rTMS targeting the dorsolateral prefrontal cortex (DLPFC) specifically improved executive function, while other cognitive domains like memory, attention, and language did not show significant benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rTMS on Parkinson's cognitive function: a systematic review and meta-analysis. Jiang, Y., Guo, Z., McClure, MA., et al.[2021]

In a study involving 27 patients with Parkinson's disease, repetitive deep transcranial magnetic stimulation (rDTMS) using H-coils was found to be safe, with no adverse events reported during 12 treatment sessions.

Patients experienced a significant improvement in motor symptoms, with an average reduction of 10.8 points on the motor UPDRS scale after treatment, indicating the potential efficacy of rDTMS as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study. Spagnolo, F., Volonté, MA., Fichera, M., et al.[2018]

Citations

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Repetitive transcranial magnetic stimulation improves ... Conclusions: rTMS can improve cognitive function, depressive symptoms, and walking ability in patients with Parkinson's disease. Keywords: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9340539/

Efficacy of repetitive transcranial magnetic stimulation in ... The results suggest that high-frequency of rTMS on primary motor cortex (M1) is effective in improving motor symptoms; while the dorsolateral ...

3. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1354864/full

Effect of different modalities of transcranial magnetic ... TMS has some long-term sustained effects on improving cognitive function in Parkinson's patients. HF-rTMS is more effective in improving cognitive function in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04707378

Navigated Repetitive Transcranial Magnetic Stimulation for ... In this study, we applied repetitive transcranial magnetic stimulation with neuronavigation to treat patients with Parkinson's disease and depression, and ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0197458019302982

A systematic review and meta-analysis of rTMS effects on ... Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to enhance cognitive functions in Alzheimer's disease and mild cognitive impairment.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1697260024000176/pdf

Efficacy and safety of repetitive Transcranial Magnetic ... High-frequency rTMS and anodal tDCS delivered for at least 2 weeks have shown improvements in cognitive function in patients with AD, maximizing performance and ...

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First German Real-World Data with a Specific H5 Coil - PMC Safety of deep repetitive transcranial magnetic stimulation (drTMS) against medical refractory symptoms in Parkinson syndromes: first German real-world data